Effects of chelating agents on oral uptake and renal deposition and excretion of cadmium

Abstract

The gastrointestinal absorption, transport, tissue deposition and excretion of cadmium was studied in adult male mice given a single oral LD50 dose of 109Cd-labeled CdCl2 alone or in combination with nitrilotriacetic acid (NTA), sodium tripolyphosphate (STPP) or ethylenediaminetetraacetic acid (EDTA). Blood, intestinal mucosa, liver and kidneys were analyzed for 109Cd at different times after exposure and the influence of the chelating agents on Cd binding to metallothionein and other tissue ligands was also studied. Acute toxicity was noted. Complex formation between Cd and EDTA was studied in solutions containing Cd:EDTA at 1:04 and 1:4 molar ratios. Adult male mice were exposed orally or by direct infusion into the stomach to either of the two solutions (containing an LD50 dose of Cd). Body retention and tissue deposition of Cd was recorded after 4 (direct infusion) or 21 days (oral exposure), and the mortality in different exposure groups observed. Adult male were also exposed to a low oral dose of 109Cd-labeled cadmium (0.5 mg/kg), followed by 18 months continuous administration of NTA, (500 ppm) STPP (500 ppm) or EDTA (50 ppm) in the drinking water or the chelating agent in combination with Cd (50 ppm), Cd alone (50 ppm) or deionized water. Whole-body retention of 109Cd, tissue deposition of 109Cd and total Cd and development of proteinuria were observed. When cadmium was given with an excess of EDTA, all Cd ions were bound in a 1:1 Cd-EDTA complex. Decreased acute toxicity was observed which was related to increased body elimination of cadmium. The Cd passes though the body still bound to EDTA and is excreted via the kidneys in this form. Similar results were found in mice exposed to Cd + NTA, while gavage of CD + STPP led to an initially decreased systemic uptake of Cd and thereafter to a prolongation of the biological half-time and thus a comparatively higher body retention of the metal. Cd may form a 2:1 complex with EDTA in the presence of excess cadmium. An increased retention and toxicity of cadmium was seen after direct infusion of this solution, while gavage resulted in a decreased toxicity. The effect of different chelating agents on acute cadmium toxicity and metabolism seemed to be due to changes in the stability of the administered chelate complexes, due to variation in pH and to the availability of metal binding ligands such as metallothionein in vivo. NTA, STPP and EDTA had no effect on the metabolism or toxicity of cadmium after long-term low dose oral exposure.

Cadmium Mobilization by Monoaralkyl‐ and Monoalkyl Esters of meso‐2,3‐Dimercaptosuccinic Acid and by a Dithiocarbamate

“…The effects of some chelating agents on the oral uptake and renal disposition of cadmium have been examined by Engstrom (1984), who also summarized some of the previous literature. Engstrom found that the molar ratio of chelating agent to cadmium in the administered solutions had a significant effect on the biological distribution of the cadmium, When the ratio was such as to form the 1:1 Cd:EDTA complex, the cadmium was found to be much less toxic than when given as the 2:l Cd:EDTA complex, and that the direct infusion of this latter complex resulted in an increased cadmium retention and toxicity.…”

Cadmium‐coordinated supramolecule suppresses tumor growth of T‐cell leukemia in mice

“…Chelating therapy is one of the most effective strategies for removing accumulated toxic metals such as cadmium from biological systems. So far, a number of chelating agents of different types have been reported as effective means of countering cadmium toxicity . Recently, we have focused on the ability of one particular supramolecule to elicit this effect.…”